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      Systemic manifestations of hepatitis C infection

      , ,

      Infectious Agents and Cancer

      BioMed Central

      HCV, Cryoglobulinemia, Autoantibodies, Lymphoma

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          Abstract

          Chronic hepatitis C (HCV) is a common infection affecting 185 million people worldwide. The most common manifestation of chronic HCV is progressive liver fibrosis, cirrhosis, liver failure and hepatocellular carcinoma. However, several systemic manifestations of HCV have been recognized and reported in the literature. The purpose of this review is to assimilate published literature based on evidence to categorize these extrahepatic manifestations with the likelihood of a causal association with HCV. Exciting recent developments have resulted in simple all oral interferon-free highly effective therapy for HCV. However, this treatment is also expensive and less accessible to most affected individuals as treatment recommendations are based on stage of liver fibrosis. Expanding the scope of HCV therapy to those with extrahepatic manifestations beyond what is currently recommended will significantly reduce the morbidity and mortality in this aging population.

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          Most cited references 74

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          Treatment of hepatitis C: a systematic review.

          Hepatitis C virus (HCV) infects more than 185 million individuals worldwide. Twenty percent of patients chronically infected with HCV progress to cirrhosis. New, simpler therapeutics using direct-acting antivirals that target various stages of the HCV life cycle are in development to eradicate HCV without concomitant interferon.
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            A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C.

            The effectiveness of hepatitis C virus (HCV) treatment with pegylated interferon and ribavirin usually is evaluated by the surrogate end point of sustained virologic response (SVR), although the ultimate goal of antiviral treatment is to reduce mortality. The impact of SVR on all-cause mortality is not well documented by HCV genotype or in populations in routine medical practice with substantial comorbidities. From the US Department of Veterans Affairs (VA), we identified all patients infected with HCV genotypes 1, 2, or 3, without human immunodeficiency virus co-infection or hepatocellular carcinoma before HCV treatment with pegylated interferon and ribavirin, who started HCV treatment from January 2001 to June 2007, stopped treatment by June 2008, and had a posttreatment HCV RNA test result of SVR or no SVR. Mortality data from VA and non-VA sources were available through 2009. HCV genotypes 1, 2, or 3 cohorts consisted of 12,166, 2904, and 1794 patients, respectively, with SVR rates of 35%, 72%, and 62%, respectively. Each cohort had high rates of comorbidities. During a median follow-up period of approximately 3.8 years, 1119 genotype-1, 220 genotype-2, and 196 genotype-3 patients died. In genotype-specific multivariate survival models that controlled for demographic factors, comorbidities, laboratory characteristics, and treatment characteristics, an SVR was associated with substantially reduced mortality risk for each genotype (genotype-1 hazard ratio, 0.70; P < .0001; genotype-2 hazard ratio, 0.64; P = .006; genotype-3 hazard ratio, 0.51; P = .0002). An SVR reduced mortality among patients infected with HCV of genotypes 1, 2, or 3 who were being treated by routine medical practice and had substantial comorbidities. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
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              Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C.

               M Olivi,  P Cacoub,  P Opolon (1999)
              To assess the prevalence of clinical and biologic extrahepatic manifestations of hepatitis C virus (HCV) infection and to identify associations between clinical and biologic manifestations. To analyze the natural history of extrahepatic manifestations of HCV infection, we reviewed only the data recorded prospectively during the first visit of 1,614 patients with chronic HCV infection, coming from a single monocenter cohort. Exclusion criteria were positivity for hepatitis B surface antigen or human immunodeficiency virus. The prevalence of dermatologic, rheumatologic, neurologic, and nephrologic manifestations; diabetes; arterial hypertension; autoantibodies; and cryoglobulins were assessed. Then, using multivariate analysis, we identified demographic, biochemical, immunologic, virologic, and liver histologic factors associated with the presence of extrahepatic manifestations. At least 1 clinical extrahepatic manifestation was observed in each of 1,202 patients (74%). Five manifestations had a prevalence >10%: arthralgia (23%), paresthesia (17%), myalgia (15%), pruritus (15%), and sicca syndrome (11%). Four biologic abnormalities had a prevalence >5%: cryoglobulins (40%), antinuclear antibodies (10%), low thyroxine level (10%), and anti-smooth muscle antibodies (7%). Only vasculitis, arterial hypertension, purpura, lichen planus, arthralgia, and low thyroxine level were associated with cryoglobulin positivity. By univariate and multivariate analyses, the most frequent risk factors for the presence of clinical and biologic extrahepatic manifestations were age, female sex, and extensive liver fibrosis. Extrahepatic clinical manifestations are frequently observed in HCV patients and involve primarily the joints, muscles, and skin. The most frequent immunologic abnormalities include mixed cryoglobulins, antinuclear antibodies, and anti-smooth muscle antibodies. The most frequent risk factors for the presence of clinical and biologic extrahepatic manifestations are advanced age, female sex, and extensive liver fibrosis.
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                Author and article information

                Contributors
                410-706-8927 , Skottilil@ihv.umaryland.edu
                Journal
                Infect Agent Cancer
                Infect. Agents Cancer
                Infectious Agents and Cancer
                BioMed Central (London )
                1750-9378
                23 May 2016
                23 May 2016
                2016
                : 11
                Affiliations
                Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, 725 W Lombard St, Room S222, Baltimore, MD USA
                Article
                76
                10.1186/s13027-016-0076-7
                4878040
                27222662
                © Tang et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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                Review
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                © The Author(s) 2016

                Oncology & Radiotherapy

                hcv, cryoglobulinemia, autoantibodies, lymphoma

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